The Neuroinflammatory Role of Pericytes in Epilepsy

Yamanaka, Gaku; Takata, Fuyuko; Kataoka, Yasufumi; Kanou, Kanako; Morıchı, Shinichiro; Dohgu, Shinya; Kawashima, Hisashi

doi:10.3390/biomedicines9070759

Cited by 28 publications

(23 citation statements)

References 108 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There were three possible mechanisms. First, neuroinflammation played an important role in epilepsy ( Yamanaka et al, 2021 ). Proinflammatory cytokines cause morphological changes in human-derived pericyte.…”

Section: Discussionmentioning

confidence: 99%

Gut Microbial Characteristics of Adult Patients With Epilepsy

et al. 2022

View full text Add to dashboard Cite

ObjectiveTo characterize the intestinal flora of patients with epilepsy and its correlation with epilepsy.MethodsPatients with ages > 18 years were consecutively enrolled from the outpatient department, Affiliated Hospital of Guizhou Medical University from January 2018 to December 2019. A total of 71 subjects were recruited, including epilepsy patients (n = 41) as an observation group and patient family members (n = 30) as a control group. Fresh stool specimens of all the subjects were collected. The 16S ribosomal RNA sequencing was analyzed to determine changes in intestinal flora composition and its correlation with epilepsy. Subgroup analysis was then conducted. All patients with epilepsy were divided into an urban group (n = 21) and a rural group (n = 20) according to the region, and bioinformatics analyses were repeated between subgroups.ResultsLEfSe analysis showed that Fusobacterium, Megasphaera, Alloprevotella, and Sutterella had relatively increased abundance in the epilepsy group at the genus level. Correlation analysis suggested that Fusobacterium sp. (r = 0.584, P < 0.01), Fusobacterium mortiferum (r = 0.560, P < 0.01), Ruminococcus gnavus (r = 0.541, P < 0.01), and Bacteroides fragilis (r = 0.506, P < 0.01) were significantly positively correlated with the occurrence of epilepsy (r ≥ 0.5, P < 0.05). PICRUSt function prediction analysis showed that there were significant differences in 16 pathways between the groups at level 3. Comparing the rural group with the urban group, Proteobacteria increased at the phylum level and Escherichia coli, Fusobacterium varium, Prevotella stercorea, and Prevotellaceae bacterium DJF VR15 increased at the species level in the rural group.ConclusionThere were significant differences in the composition and functional pathways of gut flora between epilepsy patients and patient family members. The Fusobacterium may become a potential biomarker for the diagnosis of epilepsy.

show abstract

Section: Discussionmentioning

confidence: 99%

Gut Microbial Characteristics of Adult Patients With Epilepsy

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Pericytes may act as sensors for the inflammatory response in the CNS [92,94]. Based on BBB integrity and systemic peripheral inflammation, pericytes are speculated to play a pivotal role in the pathogenesis of epilepsy during neuroinflammation [14]. Structural changes in pericytes associated with epileptic seizures are exacerbated by IL-1β rather than TNFα [95].…”

Section: Participation Of Pericytes In Migrainementioning

confidence: 99%

“…Neuroinflammation is essentially defined as an inflammatory response in the brain and spinal cord, which is modulated by the production of cytokines, chemokines, reactive oxygen species (ROS), and secondary messengers such as nitric oxide (NO) and prostaglandins [11,12]. They are mainly produced by activated microglia and astrocytes [11,12], and neurovascular units comprising neurons, pericytes, and endothelial cells [13,14]. Neuroinflammation is closely related to central nervous system (CNS) diseases, such as multiple sclerosis and epilepsy, and the regulation of cytokines has revealed new therapeutic aspects.…”

Section: Introductionmentioning

confidence: 99%

Role of Neuroinflammation and Blood-Brain Barrier Permutability on Migraine

Yamanaka

Suzuki

Morishita

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

Currently, migraine is treated mainly by targeting calcitonin gene-related peptides, although the efficacy of this method is limited and new treatment strategies are desired. Neuroinflammation has been implicated in the pathogenesis of migraine. In patients with migraine, peripheral levels of pro-inflammatory cytokines, such as interleukin-1β (IL-1β) and tumor necrosis factor-α, are known to be increased. Additionally, animal models of headache have demonstrated that immunological responses associated with cytokines are involved in the pathogenesis of migraine. Furthermore, these inflammatory mediators might alter the function of tight junctions in brain vascular endothelial cells in animal models, but not in human patients. Based on clinical findings showing elevated IL-1β, and experimental findings involving IL-1β and both the peripheral trigeminal ganglion and central trigeminal vascular pathways, regulation of the Il-1β/IL-1 receptor type 1 axis might lead to new treatments for migraine. However, the integrity of the blood-brain barrier is not expected to be affected during attacks in patients with migraine.

show abstract

“…It is notable that BBB dysfunction is observed in both human and animal studies following acute seizures, and its leakage is particularly associated with TLE (van Vliet et al, 2007 ; Marchi et al, 2012 ). As a corollary, there may be additional effects on the BBB in GBM due to the effect of epileptogenesis on pericytes, please see Löscher and Friedman ( 2020 ) and Yamanaka et al ( 2021 ) for further discussion of this work. Interestingly, epileptogenesis secondary to BBB injury largely involves the activation of inflammatory responses and reactive astrogliosis, attributes observed in the GBM microenvironment.…”

Section: Factors Contributing To Tumor-driven Epileptogenesismentioning

confidence: 99%

Converging Mechanisms of Epileptogenesis and Their Insight in Glioblastoma

Hills

Kostarelos

Wykes

2022

Front. Mol. Neurosci.

View full text Add to dashboard Cite

Glioblastoma (GBM) is the most common and advanced form of primary malignant tumor occurring in the adult central nervous system, and it is frequently associated with epilepsy, a debilitating comorbidity. Seizures are observed both pre- and post-surgical resection, indicating that several pathophysiological mechanisms are shared but also prompting questions about how the process of epileptogenesis evolves throughout GBM progression. Molecular mutations commonly seen in primary GBM, i.e., in PTEN and p53, and their associated downstream effects are known to influence seizure likelihood. Similarly, various intratumoral mechanisms, such as GBM-induced blood-brain barrier breakdown and glioma-immune cell interactions within the tumor microenvironment are also cited as contributing to network hyperexcitability. Substantial alterations to peri-tumoral glutamate and chloride transporter expressions, as well as widespread dysregulation of GABAergic signaling are known to confer increased epileptogenicity and excitotoxicity. The abnormal characteristics of GBM alter neuronal network function to result in metabolically vulnerable and hyperexcitable peri-tumoral tissue, properties the tumor then exploits to favor its own growth even post-resection. It is evident that there is a complex, dynamic interplay between GBM and epilepsy that promotes the progression of both pathologies. This interaction is only more complicated by the concomitant presence of spreading depolarization (SD). The spontaneous, high-frequency nature of GBM-associated epileptiform activity and SD-associated direct current (DC) shifts require technologies capable of recording brain signals over a wide bandwidth, presenting major challenges for comprehensive electrophysiological investigations. This review will initially provide a detailed examination of the underlying mechanisms that promote network hyperexcitability in GBM. We will then discuss how an investigation of these pathologies from a network level, and utilization of novel electrophysiological tools, will yield a more-effective, clinically-relevant understanding of GBM-related epileptogenesis. Further to this, we will evaluate the clinical relevance of current preclinical research and consider how future therapeutic advancements may impact the bidirectional relationship between GBM, SDs, and seizures.

show abstract

The Neuroinflammatory Role of Pericytes in Epilepsy

Cited by 28 publications

References 108 publications

Gut Microbial Characteristics of Adult Patients With Epilepsy

Gut Microbial Characteristics of Adult Patients With Epilepsy

Role of Neuroinflammation and Blood-Brain Barrier Permutability on Migraine

Converging Mechanisms of Epileptogenesis and Their Insight in Glioblastoma

Contact Info

Product

Resources

About